Scientists validate new lab testing platform for blood biomarkers of Alzheimer's disease

Scientists at the University of Pittsburgh have independently validated a new blood testing platform that can simultaneously measure more than 100 Alzheimer's disease biomarkers. The platform could improve clinicians' ability to grasp the multifaceted nature of Alzheimer's pathology and streamline early diagnosis of the disease. The report is published In Molecular Neurodegeneration.

“Alzheimer's disease should not be looked at through one single lens,” said lead author Thomas Karikari, Ph.D., M.Sc., assistant professor of psychiatry at Pitt. “Capturing aspects of Alzheimer's pathology in a panel of clinically validated biomarkers would increase the likelihood of stopping the disease before any cognitive symptoms emerge. »

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Early detection of pathological changes associated with Alzheimer's disease, including signs of neuroinflammation and dysfunction of cerebral blood vessel function and of nerve cell communication, is essential to improve the effectiveness of newly developed infusion treatments and to stop or slow disease progression.

Capturing a detailed snapshot of molecular changes in the brains of people at risk for Alzheimer's disease who are not yet experiencing cognitive or memory changes would allow scientists to track the progression of the disease over time and, potentially, develop guidelines for early intervention.

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However, the current system for diagnosing Alzheimer's disease is imperfect: it requires a lot of resources and time for both doctors and laboratory technicians, and can be burdensome for patients, who must repeatedly undergo invasive medical procedures.

For a proof-of-concept study, Karikari and his team tested blood samples from a cohort of 113 cognitively normal older adults living in an economically underserved area of southwestern Pennsylvania.

All samples were sent for analysis to Alamar Biosciences, the manufacturer of a new blood biomarker panel called the NULISAseq CNS Disease 120 Panel. In addition to measuring classic blood biomarkers of Alzheimer's disease, including phosphorylated forms of tau, beta-amyloid proteinthe neuroinflammation marker GFAP and the nerve cell injury marker NEFL, the panel captures changes in about 120 other proteins linked to neurodegenerative diseases.

The performance of the NULISA platform was independently validated against a series of standard Alzheimer’s disease biomarker tests for each individual sample. Changes in biomarker profiles over two years were also compared to imaging-based measures of amyloid, tau, and neurodegeneration.

According to Karikari’s assessment, the NULISAseq panel detected several biomarkers that correlated with patients’ amyloid-positive status and changes in amyloid burden over time. These biomarkers have all been previously linked to Alzheimer’s disease, but most only when measured in the cerebrospinal fluid, and included proteins associated with neuroinflammation, pathological changes in brain vasculature, and altered communication between nerve cells.

Karikari hopes the platform could be used as a tool to track changes in blood biomarkers over time in asymptomatic people and those already receiving treatment. His lab is developing a predictive model that correlates biomarker changes detected with NULISAseq with brain autopsy data and cognitive assessments collected over several years. Their goal is to identify blood biomarkers that can help stage the disease and predict his progress, both used for decision making regarding clinical management and treatment plans.